Diisopropylethylamine → 1-{2-[(1R,3S,5R)-3-(2-Fluoro-3-trifluoromethoxy-phenylcarbamoyl)-2-aza-bicyclo[3.1.0]hex-2-yl]-2-oxo-ethyl}-1H-indazole-3-carboxylic acid amide

HRID 1527600Notes

Reaction equation

HRID 1527600 reaction equation
[C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH2:13][C:14]([OH:16])=O)[N:5]=1)(=[O:3])[NH2:2].FC(F)(F)C(O)=O.[F:24][C:25]1[C:30]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:29][CH:28]=[CH:27][C:26]=1[NH:36][C:37]([C@@H:39]1[CH2:44][C@@H:43]2[C@@H:41]([CH2:42]2)[NH:40]1)=[O:38].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:24][C:25]1[C:30]([O:31][C:32]([F:35])([F:33])[F:34])=[CH:29][CH:28]=[CH:27][C:26]=1[NH:36][C:37]([C@@H:39]1[CH2:44][C@@H:43]2[C@@H:41]([CH2:42]2)[N:40]1[C:14](=[O:16])[CH2:13][N:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4]([C:1]([NH2:2])=[O:3])=[N:5]1)=[O:38]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682833421386457-64-2HCID 86673879(1R,3S,5R)-2-Aza-bicyclo[3.1.0]hexane-3-carboxylic acid (2-fluoro-3-trifluoro methoxy-phenyl)-amide trifluoroacetate

Product 1

HCID 682838291-{2-[(1R,3S,5R)-3-(2-Fluoro-3-trifluoromethoxy-phenylcarbamoyl)-2-aza-bicyclo[3.1.0]hex-2-yl]-2-oxo-ethyl}-1H-indazole-3-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of (3-carbamoyl-indazol-1-yl)-acetic acid (73.4 mg, 0.335 mmol, prepared as described in Scheme A25) in DMF (2 mL) were successively added (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-3-carboxylic acid (2-fluoro-3-trifluoromethoxy-phenyl)-amide trifluoroacetate (140 mg, 0.335 mmol), DIPEA (0.234 mL, 1.34 mmol) and HBTU (152 mg, 0.402 mmol). The reaction mixture was stirred at 25° C. for 2 h, concentrated and the residue was purified by preparative HPLC (Waters Sunfire C18-OBD, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 5% to 100% CH3CN in H2O in 20 min, 100% CH3CN 2 min, CH3CN and H2O containing 0.1% TFA). The pure fractions were combined, CH3CN was evaporated under reduced pressure and the resulting aqueous solution was lyophilized. White powder: MS: 506 [M+H]+; tR (HPLC conditions k): 3.40 min.

Workup

  1. concentrationconcentrated
  2. customthe residue was purified by preparative HPLC (Waters Sunfire C18-OBD, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 5% to 100% CH3CN in H2O in 20 min, 100% CH3CN 2 min, CH3CN and H2O containing 0.1% TFA)
  3. customCH3CN was evaporated under reduced pressure
  4. custom3.40 min.

Sources & evidence

ORD record
ord-66eefef350584916b84b62f07d0ce8a8
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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